References

1 French LE, Prins C. Toxic epidermal necrolysis. In: Dermatology

(Bolognia JL, Jorizzo JL, Rapini RP, eds). Philadelphia: Elsevier Mosby,2003; 323–31.

2 Bastuji-Garin S, Fouchard N, Bertocchi M et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000;

115:149–53.3 Guegan S, Bastuji-Garin S, Poszepczynska-Guigne E et al. Performance

of the SCORTEN during the first five days of hospitalization to pre-dict the prognosis of epidermal necrolysis. J Invest Dermatol 2006;

126:272–6.4 Lebargy F, Wolkenstein P, Gisselbrecht M et al. Pulmonary complica-

tions in toxic epidermal necrolysis: a prospective clinical study. Inten-sive Care Med 1997; 23:1237–44.

Key words: respiratory, SCORTEN, toxic epidermal necrolysis

Conflicts of interest: none declared.

Hydroxyzine-induced acute generalizedexanthematous pustulosis

DOI: 10.1111/j.1365-2133.2007.08225.x

SIR, Antihistamines are often used to treat allergic and pruritic

disorders, but there are rare reports of drug eruptions with

these agents, including several caused by the oral antihist-

amine, hydroxyzine.1–4 We report such a case.

A 73-year-old woman with psoriasis that had been well

controlled for 15 years developed a pruritic scalp lesion for

which a physician gave her an unknown medication. She

developed a rash 2 days later consisting of diffuse areas of ten-

der, oedematous erythema with hundreds of nonfollicular

pustules on her trunk and limbs. Microscopically, a biopsy

specimen from the abdomen showed spongiform subcorneal

pustules without eosinophil exocytosis and a perivascular lym-

phohistiocytic infiltrate without obvious papillary oedema or

vasculitis (Fig. 1). The patient was given intravenous methyl-

prednisolone for 9 days, and the pustules rapidly resolved

over several days with extensive desquamation. By the time of

discharge, she had only residual hyperpigmentation.

Forty days later, she was given hydroxyzine hydrochloride

(Atarax� UCB, Brussels, Belgium) for pruritic psoriatic scalp

lesions. She took one tablet and the next day again developed

diffuse erythema and pustules on her trunk and extremities,

associated with 1 day of fever. Her serum albumin was low

(2Æ8 mg dL)1) with a commensurately low serum calcium

(7Æ9 mmol dL)1), but there was no renal dysfunction. The

pustules were sterile, with no growth on culture of the con-

tents. The physician who had initially treated the patient con-

firmed that the drug she took before the first episode had

been hydroxyzine.

Patch tests were performed 1 month later, using Atarax�

tablets and each of its ingredients, cetirizine (Zyertex�) and

levocetirizine (Xyzal�) (Table 1). The patient had positive

reactions (++) at 48 h to Atarax� tablets and hydroxyzine

2Æ5% pet. The aqueous formulations produced irritated ery-

thema. By 72 h, the reactions to Atarax� and to hydroxyzine

in all formulations tested were positive (++) with pustules

(Fig. 2). There was also focal flaring in previously involved

areas. None of the other ingredients in Atarax�, or cetirizine

or levocetirizine, induced a positive reaction. Five control sub-

jects had negative patch tests with Atarax� tablets and

hydroxyzine (2Æ5% pet.).

Hydroxyzine is often used to treat allergic diseases, but this

case is a reminder that serious hypersensitivity reactions are

possible even with an antihistamine. Acute generalized exan-

thematous pustulosis (AGEP) typically has hundreds of widely

distributed nonfollicular pustules on an oedematous, erythem-

atous base, predominantly in the intertriginous areas.5 It

resolves quickly, often in less than 15 days. The fact that the

eruption is drug-induced in a particular case can be confirmed

Fig 1. Histopathological finding showing spongiform subcorneal

pustules without eosinophil exocytosis (haematoxylin and eosin;

original magnification · 200).

Table 1 Patch-test results

Ingredient Concentration

Time of exposure

48 h 72 h 7 days

Cetirizine As is ) ) )Levocetirizine As is ) ) )Hydroxyzine 2% aq1,3 IR ++, pustulos P

5% aq1,3 IR ++, pustulos P10% aq1,3 IR ++, pustulos P

2Æ5% pet4 ++ ++, pustulos PColloidal silica 5% aq1,3 ) ) )

As is ) ) )Macrocrystalline

cellulose

5% aq1,3 ) ) )As is ) ) )

Magnesium stearate As is1,3 ) ) )Lactose 20% aq1,3 ) ) )

Pet, petrolatum; aq, aqueous; IR, irritated erythema; P, pigmen-

tation.

� 2007 The Authors

Journal Compilation � 2007 British Association of Dermatologists • British Journal of Dermatology 2007 157, pp1267–1304

1296 Correspondence

by patch testing. In this case, hydroxyzine in petrolatum

yielded a more clear-cut reaction than did the various aqueous

preparations, so we suggest using a 2Æ5% pet. preparation if

patch testing is indicated. Hydroxyzine has been reported to

cause a generalized maculopapular eruption,1–4 but we were

unable to find any published reports of hydroxyzine-induced

AGEP.

Y-S . T SA I*

M-E . TU*

Y-H. WU*�Y-C. L IN*�

*Department of Dermatology, Mackay

Memorial Hospital, 92, Sec 2, Chung-Shan N Rd,

Taipei 10449, Taiwan

�Mackay Medicine, Nursing and

Management College and �Lee-Ming

Institute of Technology, Tapei, Taiwan

Correspondence: Mei-Eng Tu.

E-mail: tme@ms2.mmh.org.tw

References

1 Michel M, Dompmartin A, Louvet S et al. Skin reactions to hydroxy-zine. Contact Dermatitis 1997; 36:147–9.

2 Ash S, Scheman AJ. Systemic contact dermatitis to hydroxyzine. Am JContact Dermat 1997; 8:2–5.

3 Lew BL, Haw CR, Lee MH. Cutaneous drug eruption from cetirizine

and hydroxyzine. J Am Acad Dermatol 2004; 50:953–6.4 Dalmau J, Serra-Baldrich E, Roe E et al. Skin reaction to hydroxyzine

(Atarax�) patch test utility. Contact Dermatitis 2006; 54:216–17.5 Sidoroff A, Halevy S, Bavinck JN et al. Acute generalized exanthema-

tous pustulosis (AGEP) – a clinical reaction pattern. J Cutan Pathol2001; 28:113–19.

Key words: acute generalized exanthematous pustulosis, hydroxyzine

Conflicts of interest: none declared.

Malignant melanoma in a woman withLEOPARD syndrome: identification of agermline PTPN11 mutation and a somaticBRAF mutation

DOI: 10.1111/j.1365-2133.2007.08229.x

SIR, LEOPARD syndrome (LS) is a congenital developmental

disorder and is an acronym for multiple lentigines, electro-

(a) (b)

(c) (d)

Fig 2. Patch-test results: positive (++) reaction with pustules to Atarax� tablet at 48 h (a) and 72 h (b), and to hydroxyzine 2Æ5% pet. at 48 h

(c) and 72 h (d).

� 2007 The Authors

Journal Compilation � 2007 British Association of Dermatologists • British Journal of Dermatology 2007 157, pp1267–1304

Correspondence 1297